Summary of Work: Interleukin-2 (IL-2) is a cytokine with important regulatory properties for both T and B cells. The current studies were undertaken to evaluate interleukin-2 in the treatment of HIV infection. Our studies initially focused on patients with CD4 counts of about 200 cells/mm3 we administered IL-2 for 5 days approximately every two months at doses ranging from 6 to 18 million units/d. The courses of IL-2 were well-tolerated, although most of the patients required dosage reductions due to IL-2-related adverse effects. Sustained improvement in CD4 numbers was seen primarily in patients with >200 CD4 cells/mm3. There also was a transient increase in viral load as measured by the ratted assay seen at day 6-day 8 following initiation of IL-2 therapy. Responses in CD4 number were less common in patients with lower baseline CD4 counts. Based on the preliminary results seen in our open trial, we undertook a randomized trial to evaluate IL-2 therapy in patients with CD4 counts above 200 cells/mm in combination with currently approved anti- retroviral therapies. The study opened in April 1993 and was completed in February of 1995. with 60 patients enrolling. This study also showed in a controlled setting that intermittent therapy with IL-2 can lead to a substantial and sustained increase in CD4 cell counts without leading to an increase in plasma viral load. More recently, we have focused on improving the tolerance of IL-2, by decreasing the dose and duration of therapy, and by evaluating alternative methods of administering IL-2. We are currently developing an extension phase of ongoing studies to determine whether administration of corticosteroids with IL2 can lead to improved tolerance of IL-2 without interfering with the immunomodulatory effects. These studies are potentially important because they are the first ones to suggest that immunomodulating agents combined with anti-retroviral agents may have a benefit in patients with HIV infection.